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Possible long term neurotoxic effects due to administration of ketamine or propofol in combination with ionising radiation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2023 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The brain is one of the first organs that start to differentiate in an embryo and even small disturbances could have a major impact on the brain development during the susceptible period called the brain growth spurt. This period starts during the last trimester of pregnancy in humans and climaxes at birth, while it starts postnatally in mice and climaxes at post-natal day 10 (PND10). Nevertheless, radiation is needed in radiotherapy for treating brain tumours. In combination with that, analgesics are often used in children to give a more precise treatment and prevent stress. This is a growing issue, since studies show that administration of propofol or ketamine in combination with radiation could cause behavioural changes in mouse models if administered during the brain development. 

 

The aim of this thesis was to study the long-term effects that could be found 12 months after exposure to a combination of ketamine or propofol and radiation at PND10, and if this could explain the behavioural changes that have been seen in mice after administration of propofol or ketamine in combination with radiation. 

 

The method that was used for this study was RT-qPCR, using SYBR green as a dye. The study was done on male mice of the following exposure groups: Control with 0,9% saline, 7,5mg/kg ketamine, 10mg/kg propofol, 200mGy whole-body radiation, ketamine + radiation and propofol + radiation. Four genes were examined and Rplp0 was used as a housekeeping gene. The studied genes were Nrf2 and Keap1, which were indicators of oxidative stress, while BDNF and Grin2b were specific for neural function. 

 

As a result, the statistical analysis did not show any statistical significance regarding changes in gene expression of Nrf2 (exposure to ketamine p=0,6079; exposure to propofol p=0,5153), Keap1 (exposure to ketamine p= 0,5526; exposure to propofol p=0,3295), BDNF (Exposure to ketamine p=0,6133; exposure to propofol p=0,4615), and Grin2b (exposure to ketamine p= 0,5522; exposure to propofol p=0,5310). 

 

To conclude, this study could not find any alterations regarding gene expression of the above-mentioned genes, explaining the behavioural changes that have been seen in previous studies. 

Place, publisher, year, edition, pages
2023. , p. 38
Keywords [en]
Ketamine, propofol, radiation, neurodegeneration, gene expression, Keap1, Grin2b, BDNF, Nrf2, Rplp0.
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-495919OAI: oai:DiVA.org:uu-495919DiVA, id: diva2:1733996
Subject / course
Toxicology
Educational program
Master of Science Programme in Pharmacy
Supervisors
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Available from: 2023-02-08 Created: 2023-02-03 Last updated: 2023-02-08Bibliographically approved

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